A complex interplay among virus, dendritic cells, T cells, and cytokines in dengue virus infections.
Severe dengue virus (DV) infections can cause the life-threatening condition dengue hemorrhagic fever, which is characterized by a severe plasma leak, thrombocytopenia, hemorrhage, and, in severe cases, circulatory collapse and death. There is now much evidence that pre-existing immunity to DV can enhance disease when an individual becomes infected on a second or sequential occasion. It has been shown that in contrast to infected dendritic cells (DC), noninfected bystander DC underwent maturation in dengue infection. In this study, we show that TNF-alpha and type I IFN contribute to the maturation of bystander DC, whereas the inhibition of DV-infected DC maturation can be overcome by activated T cells. Furthermore, IFN-gamma-inducible chemokines, CXCL9, 10, and 11 produced by infected DC are greatly amplified in the presence of DV-specific T cells. The chemokine secretion is also enhanced in coculture of HUVEC with either DV-infected DC or activated T cells. Finally, we found a close correlation between the serum level of these three chemokines and disease severity.
Dejnirattisai
Wanwisa
W
Department of Immunology, Division of Medicine, Hammersmith Hospital, Imperial College, London, United Kingdom.
Duangchinda
Thaneeya
T
Lin
Chen-Lung Steve
CL
Vasanawathana
Sirijitt
S
Jones
Meleri
M
Jacobs
Michael
M
Malasit
Prida
P
Xu
Xiao-ning
XN
Screaton
Gavin
G
Mongkolsapaya
Juthathip
J
D024201:Bystander Effect / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D003715:Dengue / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D003716:Dengue Virus / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte